While muscular dystrophy (MD) used to define a single type of muscle disorder, it now encompasses more than 150 genetic subtypes of muscular diseases. At least that many genes are associated with progressive muscle disorders, and in the past 20 years, physicians have experienced an explosion in their knowledge of the genetic underpinnings of MD and disorder subtypes. For example, in the case of limb-girdle muscular dystrophy (LGMD), the fourth most common type of genetic muscle disease, scientists used to recognize only a single overarching category; now, there are at least 50 genes identified in causing disorders in a limb-girdle distribution, leading to a more refined classification and specific treatment options.

Penn State Hershey Medical Center conducts a large amount of clinical research in the genetic roots of muscle disease, and is internationally-renowned for its clinical expertise in LGMD, according to Matthew P. Wicklund, M.D., professor of neurology and pediatrics. In fact, after reviewing more than 3,000 articles over four years, Wicklund, along with nine other experts, published a definitive guideline on diagnosis and management of LGMD in October 2014.1 Many acquired and genetic muscle diseases present as weakness in the hip girdle, thighs, shoulder girdle and proximal arms, the classic “limb-girdle” pattern.2 Part of Wicklund’s responsibility is to further subtype those patients.

MRI of the calves in a patient with LGMD type 2B dysferlinopathy. Relative preservation of muscle in the anterior compartment (single arrows) of the forelegs is compared to marked fatty and fibrous replacement in the posterior compartment (double arrows).3

This genetic classification is important for several reasons, says Wicklund. “To clarify the pattern of inheritance for future generations, one must know if the patient has dominantly- or recessively-inherited MD,” he continues. Additionally, despite not yet having treatments for the underlying musculoskeletal components of MD, they do for cardiac or pulmonary involvement, which is associated with approximately 50 percent of MD genetic subtypes. Finally, precise genetic classification of MD can help clinicians avoid unnecessary treatments and lead to proactive management of the disease, such as physical and occupational therapy, pacemaker-defibrillators for arrhythmias, and noninvasive positive airway pressure for ventilatory failure.2

At Penn State Hershey Neuroscience Institute, specialists treat nearly 500 MD patients per year, with a relatively even mix of adult and pediatric patients. The Institute is working with a genetic testing organization to determine the prevalence of LGMD in the United States (close to 5,000 patients) and is involved in numerous clinical trials, including gene therapy, likely to be a viable pathway for treatment in all types of MD. Wicklund views the expansion in genetic diagnoses as one of the most important recent developments in MD care, and is eager to explore the ability to translate this information into genetic modifications that could potentially alter the course of these diseases.